超高齢化社会を迎えた現代において、生体材料や再生医学の分野に対する社会的要請 は非常に高い。しかし、これらの分野はやや停滞の様相を呈しており、その原因としては経験 論や現象論に基づいた応用研究が主流となっていることが挙げられる。そこで本研究では、
HA がなぜ骨伝導を示すのかという極めて基本的な事象を解明することで、これらの分野に対 するブレークスルーの提案を目指した。実際に、タンパク質の吸着特性ならびに細胞応答の 観点から、骨伝導を示す材料であるHAと骨伝導を示さない材料である-Al2O3との差異を解 析することにより、骨伝導材料が満たすべき条件について以下の5つの知見を得た。
1) アルブミン吸着能が低いこと。本研究で調べた限りでは、材料のアルブミン吸着能が生体
環境下で3 mg/m2未満の場合に、その材料は骨伝導を示した。
2) 局所的に正に帯電した部位を有し、その結果として以下のa)およびb)を満たすこと。
a) その部位とアルブミンが有するグルタミン酸残基やアスパラギン酸残基の COO-基と の間にイオン間相互作用を及ぼし、アルブミンを特異的に吸着すること。
b) その部位と OPN が有するポリアスパラギン酸配列の COO-基との間にイオン間相互 作用を及ぼし、OPN を特異的に吸着すること。またその結果として、OPN が有する RGD配列を露出させること。
HAであればa面のCa2+サイトが、-Al2O3であればルイス酸サイトがこの部位に該当する と考えられる。
3) インプラント時に、アルブミンを吸着するよりも先に骨芽細胞を接着すること。これは、アル ブミンが示す骨芽細胞接着阻害作用を回避することに相当する。本研究で調べた限りで は、インプラント開始から1時間以内に2000 cells/cm2程度（見かけ面積）の骨芽細胞を接 着すると、その材料は骨伝導を示した。
4) アルブミンの吸着によって、単球・マクロファージ系細胞の接着が阻害されないこと。この 要因としては、2)で述べたアルブミンの特異的な吸着が考えられる。
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5) OPN吸着能が低いこと。本研究で調べた限りでは、材料のOPN吸着能が生体環境下で
5 mg/m2未満の場合に、その材料は骨伝導を示した。
しかし、上記の知見はあくまでも骨伝導機構のごく一端を解明したに過ぎない。今後の課題 としては大きく分けて以下の2点が挙げられる。1つは他のタンパク質に関する検討である。表 1の中で我々は4 種類のタンパク質に着目したが、本報告では主にアルブミンしか取り扱って いない。そこで今後は、フィブロネクチン、オステオポンチンならびにオステオカルシンについ てアルブミンと同様の実験を施行し、それぞれのタンパク質が骨伝導の発現においてどの様 な役割を果たしているかを検討する必要がある。
2 つめは他の材料に関する検討である。本報告の中では、骨伝導を示す材料としては主に
HA、骨伝導を示さない材料としては-Al2O3しか取り扱っていない。しかし、他にも骨伝導を示
す（可能性のある）材料としては-Al2O3、-TCP ならびにリン酸八カルシウムなどが挙げられ、
一方の骨伝導を示さない材料は数多く存在する。そこで今後は、これらの材料について HA や-Al2O3 と同様に実験を施行し、それぞれの材料が示す特徴を比較することで、骨伝導材 料に求められる条件を絞り込む必要がある。
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